Are treatment targets for hypercholesterolemia evidence based? Systematic review and meta-analysis of randomised controlled trials (original) (raw)
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Atherosclerosis, 2007
Aims: To assess efficacy and safety of HMG-CoA reductase inhibitor (statin) treatment in children and adolescents with heterozygous familial hypercholesterolaemia. Methods: MEDLINE, EMBASE, COCHRANE and Current Controlled Trials databases were searched. Study design, efficacy, and safety outcome-measures were extracted. Results of parallel-group randomised placebo controlled trials with low density (LDL) and high density lipoprotein cholesterol (HDL), and triglycerides as outcomes were pooled using standard meta-analytical methods. Results: One hundred and fifty seven of 1060 identified papers studied familial hypercholesterolaemia, and 18 papers reported 7 prospective case series, 1 non-randomised trial, 2 trials with active treatment control groups, and 8 parallel-group randomised placebo controlled trials (RCT). The RCTs randomised 947 children, aged 8-18 years, for periods of 6-96 weeks with an estimated 850 person-years follow-up. There were no differences in clinical or laboratory adverse reactions between placebo and active treatment. Statins lowered LDL 32.5% (95% CI 24.3, 40.7), increased HDL 3.4% (0.8, 6.0), lowered triglycerides 3.0% (−11.6, 17.6), attenuated progression of carotid medial thickness, and improved endothelial function. Conclusions: Statin monotherapy is efficacious, well tolerated and safe in the short-term, although long-term safety remains unclear. Current evidence supports treatment of children at highest cardiovascular risk, but results of ongoing , longer-term studies may extend these indications.
Vascular health and risk management, 2011
Children who appear healthy, even if they have one or more recognized cardiovascular risk factors, do not generally have outcomes of cardiovascular or other vascular disease during childhood. Historically, pediatric medicine has not aggressively screened for or treated cardiovascular risk factors in otherwise healthy children. However, studies such as the P-Day Study (Pathobiological Determinants of Atherosclerosis in Youth), and the Bogalusa Heart Study, indicate that healthy children at remarkably young ages can have evidence of significant atherosclerosis. With the increasing prevalence of pediatric obesity, can we expect more health problems related to the consequences of pediatric dyslipidemia, hypertriglyceridemia, and atherosclerosis in the future? For many years, medications have been available and used in adult populations to treat dyslipidemia. In recent years, reports of short-term safety of some of these medications in children have been published. However, none of these...
Journal of Clinical Lipidology, 2015
This thesis has emerged from my work since 2002 at the Lipid Clinic, Rikshospitalet, Oslo University Hospital. The Lipid Clinic was started in 1984 by pediatrician Leiv Ose, to care for children with familial hypercholesterolemia and their parents. In my work at the Clinic I have had the privilege to follow these families. My main task has been to be responsible for performing clinical trials with new lipid lowering drugs. In addition, I have followed up children and adults in the regular outpatient clinic. My professional background is mainly from family medicine, having worked for 20 years as a family physician before I was employed at the Lipid Clinic. I am very grateful to Leiv Ose for having employed me, giving me the opportunity to explore this, for me, new field of medicine in the final part of my professional career, and for guiding me into the world of lipidology and clinical trials. Special thanks also to my colleague since 2002, Kjetil Retterstøl, for having taught me the fundamentals in lipidology and for always fruitful, inspiring and humorous discussions. For many years, Martin Prøven Bogsrud has been very important to me as a colleague, research fellow and discussion partner, and he has undertaken the task to appoint opponents for this thesis. Since 2014, Martin has been the leader for the newly established National Advisory Unit on familial hypercholesterolemia (NKT for FH). The National Advisory Unit has directly supported my work by employing me part-time and by establishing the treatment registry which our paper V is based on. Kirsten Holven, who is head of research in the National Advisory Unit is an important discussion partner, research partner, has provided significant feedback on this thesis and has been guiding me in the submission process. Arne Svilaas, colleague at the Lipid Clinic since 2002, has been an important discussion partner and provided valuable feedback. All the above mentioned persons have served as a counselling group in the work with the thesis.
Jama, 2004
Background-A multicenter, randomized, double-blind, placebo-controlled study was conducted to evaluate LDL cholesterol-lowering efficacy, overall safety, and tolerability and the influence on growth and pubertal development of simvastatin in a large cohort of boys and girls with heterozygous familial hypercholesterolemia (heFH). Methods and Results-A total of 173 heFH children (98 boys and 75 girls) were included in this study. After a 4-week diet/placebo run-in period, children with heFH were randomized to either simvastatin or placebo in a ratio of 3:2.
Acc Current Journal Review, 2004
Background-A multicenter, randomized, double-blind, placebo-controlled study was conducted to evaluate LDL cholesterol-lowering efficacy, overall safety, and tolerability and the influence on growth and pubertal development of simvastatin in a large cohort of boys and girls with heterozygous familial hypercholesterolemia (heFH). Methods and Results-A total of 173 heFH children (98 boys and 75 girls) were included in this study. After a 4-week diet/placebo run-in period, children with heFH were randomized to either simvastatin or placebo in a ratio of 3:2.
Efficacy and Safety of Statin Therapy in Children With Familial Hypercholesterolemia
Circulation, 2002
Background— A multicenter, randomized, double-blind, placebo-controlled study was conducted to evaluate LDL cholesterol–lowering efficacy, overall safety, and tolerability and the influence on growth and pubertal development of simvastatin in a large cohort of boys and girls with heterozygous familial hypercholesterolemia (heFH). Methods and Results— A total of 173 heFH children (98 boys and 75 girls) were included in this study. After a 4-week diet/placebo run-in period, children with heFH were randomized to either simvastatin or placebo in a ratio of 3:2. Simvastatin was started at 10 mg/d and titrated at 8-week intervals to 20 and then 40 mg/d. During a 24-week extension period, the patients continued to receive simvastatin (40 mg) or placebo according to their assignment. After 48 weeks of simvastatin therapy, there were significant reductions of LDL cholesterol (−41%), total cholesterol (−31%), apolipoprotein B (−34%), VLDL cholesterol (−21%), and triglyceride (−9%) levels. HDL...
Atherosclerosis, 2013
In the heterozygous form of familial hypercholesterolemia (FH), blood concentrations of low-density lipoprotein cholesterol (LDL-C) are elevated two to three times above the normal range since birth, and cause strongly elevated risk of premature coronary artery disease (CAD). There is no evidence that statin therapy is unsafe in FH children, and it has not been associated with clinically significant changes in measures of growth or maturation, liver enzymes, serum creatine kinase, or incidence of myopathy. However, the opinions among clinicians, and between countries, about the age at which statin therapy should be initiated in FH children vary. This review attempts to critically examine the available data, so that clinically the most appropriate age of initiating statin treatment in FH children as a preventive measure for future CAD could be established.
A systematic review and meta-analysis on screening lipid disorders in the pediatric age group
Journal of Research in Medical Sciences, 2015
lipoprotein cholesterol (LDL-C) as well as low concentration of high-density lipoprotein cholesterol (HDL-C) are important risk factors of CVD in adults. [1-4] The accumulating number of studies confirmed the tracking of CVD risk factors including dyslipidemia from childhood to adulthood. [3,4] They showed that about 50% of children and adolescents with dyslipidemia will continue to have this disorder as adult. [3-5] TC levels increase from birth, stabilize at about 2 years of age, reach a peak before puberty, and then turn down slightly during adolescence. Normal values for lipids in Background: Different viewpoints exist about lipid screening in all children or only in children with positive family history (FH) of premature cardiovascular diseases (CVDs) or hypercholesterolemia. This systematic review and meta-analysis aim to assess the effectiveness of lipid screening in children and adolescents according to the existence of positive FH of CVD risk factors. Materials and Methods: PubMed, Scopus, and Google scholar were searched to identify relevant papers that were published from November 1980 until 30 November 2013. Irrelevant studies were set aside after studying their title, abstract, and full text. Then, the relevant studies were assessed by using a quality appraisal checklist. We used random effect model for meta-analysis and calculating the total estimation of sensitivity, specificity, and the positive predictive value (PPV) of FH in predicting dyslipidemia among children and adolescents. Results: Overall, 17,214 studies were identified in the primary search, out of which 19 primary studies were qualified for study entry. The sensitivity of positive FH of premature CVD or dyslipidemia for predicting dyslipidemia among children varied between 15 and 93. Moreover, the effectiveness of screening children for dyslipidemia according to premature CVD or dyslipidemia in their relatives was low in 86.9% of the primary studies. The total estimation of sensitivity, specificity, and predictive value was 42.6, 59, and 20.7, respectively, according to the meta-analysis results. Conclusion: The present meta-analysis indicated that selecting target population for screening children and adolescents for dyslipidemia according to their FH has low sensitivity.